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WO2009146539A8 - 4-(aminomethyl)cyclohexanamine derivatives as calcium channel blockers - Google Patents

4-(aminomethyl)cyclohexanamine derivatives as calcium channel blockers Download PDF

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Publication number
WO2009146539A8
WO2009146539A8 PCT/CA2009/000767 CA2009000767W WO2009146539A8 WO 2009146539 A8 WO2009146539 A8 WO 2009146539A8 CA 2009000767 W CA2009000767 W CA 2009000767W WO 2009146539 A8 WO2009146539 A8 WO 2009146539A8
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WO
WIPO (PCT)
Prior art keywords
calcium channel
cyclohexanamine
aminomethyl
derivatives
channel blockers
Prior art date
Application number
PCT/CA2009/000767
Other languages
French (fr)
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WO2009146539A1 (en
Inventor
Hassan Pajouhesh
Ramesh Kaul
Mike Grimwood
Jason Tan
Yuanxi Zhou
Original Assignee
Neuromed Pharmaceuticals Ltd.
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Publication date
Application filed by Neuromed Pharmaceuticals Ltd. filed Critical Neuromed Pharmaceuticals Ltd.
Priority to CA2722723A priority Critical patent/CA2722723A1/en
Publication of WO2009146539A1 publication Critical patent/WO2009146539A1/en
Publication of WO2009146539A8 publication Critical patent/WO2009146539A8/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
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    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract

Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted T-type calcium channel activity are disclosed. Specifically, a series of compounds containing 4-(aminomethyl)cyclohexanamine derivatives as shown in formula (1).
PCT/CA2009/000767 2008-06-02 2009-06-02 4-(aminomethyl)cyclohexanamine derivatives as calcium channel blockers WO2009146539A1 (en)

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Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8362021B2 (en) * 2006-05-11 2013-01-29 Zalicus Pharmaceuticals Ltd. Method for increasing the bioavailability of benzhydryl piperazine containing compounds
US8377968B2 (en) 2008-06-02 2013-02-19 Zalicus Pharmaceuticals, Ltd. N-piperidinyl acetamide derivatives as calcium channel blockers
US8273900B2 (en) 2008-08-07 2012-09-25 Novartis Ag Organic compounds
CA2771612A1 (en) * 2009-09-18 2011-03-24 Zalicus Pharmaceuticals Ltd. Selective calcium channel modulators
US8394858B2 (en) 2009-12-03 2013-03-12 Novartis Ag Cyclohexane derivatives and uses thereof
EP2531490B1 (en) * 2010-02-02 2014-10-15 Novartis AG Cyclohexyl amide derivatives as crf receptor antagonists
JP5921555B2 (en) * 2010-09-29 2016-05-24 エスケー バイオファーマシューティカルズ カンパニー リミテッド Novel methylcyclohexane derivatives and their use
JP5749480B2 (en) * 2010-12-08 2015-07-15 東京応化工業株式会社 New compounds
US8409560B2 (en) 2011-03-08 2013-04-02 Zalicus Pharmaceuticals Ltd. Solid dispersion formulations and methods of use thereof
CA2828610A1 (en) 2011-03-08 2012-09-13 Zalicus Pharmaceuticals Ltd. Solid dispersion formulations and methods of use thereof
EP2567959B1 (en) 2011-09-12 2014-04-16 Sanofi 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
EP2822944A1 (en) 2012-03-05 2015-01-14 Amgen, Inc. Oxazolidinone compounds and derivatives thereof
WO2014134306A1 (en) 2013-03-01 2014-09-04 Zalicus Pharmaceuticals, Ltd. Heterocyclic inhibitors of the sodium channel
EP3150598B1 (en) 2014-05-28 2019-02-13 TOA Eiyo Ltd. Substituted tropane derivatives
MX2017005462A (en) 2014-11-05 2017-07-28 Flexus Biosciences Inc Immunoregulatory agents.
UY36390A (en) 2014-11-05 2016-06-01 Flexus Biosciences Inc MODULATING COMPOUNDS OF INDOLAMINE ENZYME 2,3-DIOXYGENASE (IDO), ITS SYNTHESIS METHODS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
US11273218B2 (en) 2015-10-22 2022-03-15 Cavion, Inc. Methods for treating Angelman syndrome and related disorders
JOP20190024A1 (en) 2016-08-26 2019-02-19 Gilead Sciences Inc Substituted pyrrolizine compounds and uses thereof
CA3053781A1 (en) 2017-02-15 2018-08-23 Cavion, Inc. Benzopyran and naphalene derivatives and their uses as calium channel inhibitors
CA3061720A1 (en) 2017-04-26 2018-11-01 Cavion, Inc. Methods for improving memory and cognition and for treating memory and cognitive disorders
WO2019165374A1 (en) 2018-02-26 2019-08-29 Gilead Sciences, Inc. Substituted pyrrolizine compounds as hbv replication inhibitors
AU2019355021B2 (en) 2018-10-03 2024-09-12 Cavion, Inc. Treating essential tremor using (R)-2-(4-Isopropylphenyl)-N-(1-(5-(2,2,2-Trifluoroethoxy)pyridin-2-yl)ethyl)acetamide
EP3996746A4 (en) 2019-07-11 2023-08-23 Praxis Precision Medicines, Inc. T-TYPE CALCIUM CHANNEL MODULATOR FORMULATIONS AND METHODS OF USE THEREOF
WO2023192665A2 (en) * 2022-04-01 2023-10-05 Praxis Precision Medicines, Inc. T-type calcium channel modulators and methods of use thereof

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990005723A1 (en) * 1988-11-24 1990-05-31 Yoshitomi Pharmaceutical Industries, Ltd. Trans-4-amino(alkyl)-1-pyridylcarbamoyl-cyclohexane compounds and their medicinal use
US5989920A (en) * 1994-12-02 1999-11-23 Synaptic Pharmaceutical Corporation Methods of modifying feeding behavior compounds useful in such methods and DNA encoding a hypothalmic atypical neuropeptide Y/peptide YY receptor Y5
AU3295297A (en) * 1996-06-04 1998-01-05 Synaptic Pharmaceutical Corporation Methods of modifying feeding behavior, compounds useful in such methods, and dna encoding a hypothalamic atypical neuropeptide y/peptide yy receptor (y5)
US20030125269A1 (en) * 1998-08-26 2003-07-03 Ming Li T-type calcium channel
WO2003018563A1 (en) * 2001-08-31 2003-03-06 Northwestern University Anti-inflammatory and protein kinase inhibitor composition and method of use
CA2460594A1 (en) * 2001-10-01 2003-04-10 Taisho Pharmaceutical Co., Ltd. Mch receptor antagonists
KR100534556B1 (en) * 2001-10-26 2005-12-08 주식회사 오리엔트바이오 Method for resistance of epilepsy by suppressing the function of alpha 1G protein
KR20030037081A (en) * 2001-11-02 2003-05-12 한국과학기술연구원 Method for the suppression of visceral pain by regulating T-type calcium channel
GB0126781D0 (en) * 2001-11-07 2002-01-02 Medical Res Council Modulation
US20060003985A1 (en) * 2002-10-17 2006-01-05 Renger John J Enhancement of sleep with t-type calcium channel antagonists
JP2007520996A (en) * 2003-01-15 2007-08-02 ミレニアム・ファーマシューティカルズ・インコーポレイテッド 44390, 54181, 211, 5687, 884, 1405, 636, 4421, 5410, 30905, 2045, 16405, 18560, 2047, 33751, 52721, 14063, 20739, 32544, 43239, 44373, 51164, 53010, 16852, 1587, 2207, 22245, 2387, 52908, 69112, 14990, 18547, 115, 579, 15985, 15625, 760, 18603, 2395, 2554, 8675, 32720, 4809, 14303, 16816, 17827, 32620, 577, 619, 1423, 2158, 8263, 15402, 16209, 16386, 21165, 30911, 41897, 1643, 2543, 9626, 13 31,32409,84260,2882,8203,32678 or methods and compositions for treating urological disorders using 55,053
JP2006522109A (en) * 2003-03-31 2006-09-28 大正製薬株式会社 Novel quinazoline derivatives and therapeutic methods related to their use
DE102004023507A1 (en) * 2004-05-10 2005-12-01 Grünenthal GmbH Substituted cyclohexylacetic acid derivatives
US20080090863A1 (en) * 2004-09-30 2008-04-17 Taisho Pharmaceutical Co., Ltd. Pyridine Derivatives and Their Use as Medicaments for Treating Diseases Related to Mch Receptor

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